N-Sulfonyl-aminobiaryls as Antitubulin Agents and Inhibitors of Signal Transducers and Activators of Transcription 3 (STAT3) Signaling

详细信息    查看全文

• 作者：Mei-Jung Lai ; Hsueh-Yun Lee ; Hsun-Yueh Chuang ; Li-Hsun Chang ; An-Chi Tsai ; Mei-Chuan Chen ; Han-Lin Huang ; Yi-Wen Wu ; Che-Ming Teng ; Shiow-Lin Pan ; Yi-Min Liu ; Samir Mehndiratta ; Jing-Ping Liou
• 刊名：Journal of Medicinal Chemistry
• 出版年：2015
• 出版时间：August 27, 2015
• 年：2015
• 卷：58
• 期：16
• 页码：6549-6558
• 全文大小：437K
• ISSN：1520-4804

文摘

A series of N-sulfonyl-aminobiaryl derivatives have been examined as novel antitubulin agents. Compound 21 [N-(4鈥?cyano-3鈥?fluoro-biphenyl-2-yl)-4-methoxy-benzenesulfonamide] exhibits remarkable antiproliferative activity against four cancer cell lines (pancreatic AsPC-1, lung A549, liver Hep3B, and prostate PC-3) with a mean GI₅₀ value of 57.5 nM. Additional assays reveal that 21 inhibits not only tubulin polymerization but also the phosphorylation of STAT3 inhibition with an IC₅₀ value of 0.2 渭M. Four additional compounds (8, 10, 19, and 35) are also able to inhibit this phosphorylation. This study describes novel N-sulfonyl-aminobiaryl (biaryl-benzenesulfonamides) as potent anticancer agents targeting both STAT3 and tubulin.